Time to positivity in bloodstream infection is not a prognostic marker for mortality: analysis of a prospective multicentre randomized control trial

Fergus Hamilton; Rebecca Evans; Peter Ghazal; Alasdair MacGowan

doi:10.1016/j.cmi.2021.05.043

Time to positivity in bloodstream infection is not a prognostic marker for mortality: analysis of a prospective multicentre randomized control trial

Clin Microbiol Infect. 2022 Jan;28(1):136.e7-136.e13. doi: 10.1016/j.cmi.2021.05.043. Epub 2021 Jun 7.

Authors

Fergus Hamilton¹, Rebecca Evans², Peter Ghazal³, Alasdair MacGowan⁴

Affiliations

¹ Infection Sciences, Pathology, North Bristol NHS Trust, Bristol, UK; Population Health Sciences, University of Bristol, Bristol, UK; Project Sepsis, Cardiff University, Cardiff, UK. Electronic address: Fergus.Hamilton@bristol.ac.uk.
² Bristol Trials Centre, Bristol Medical School, University of Bristol, Bristol, UK. Electronic address: becci.evans@bristol.ac.uk.
³ Project Sepsis, Cardiff University, Cardiff, UK. Electronic address: ghazalp@cardiff.ac.uk.
⁴ Infection Sciences, Pathology, North Bristol NHS Trust, Bristol, UK. Electronic address: alasdair.macgowan@nbt.nhs.uk.

PMID: 34111588
DOI: 10.1016/j.cmi.2021.05.043

Abstract

Objectives: Time to positivity (TTP), calculated automatically in modern blood culture systems, is considered a proxy for microbial load and has been suggested as a potential prognostic marker in bloodstream infections. In this large, multicentre, prospectively collected cohort, our primary analysis aimed to quantify the relationship between the TTP of monomicrobial blood cultures and mortality.

Methods: Data from a multicentre randomized controlled trial (RAPIDO) in bloodstream infection were analysed. Bloodstream infections were classified into 13 groups/subgroups. The relationship between mortality and TTP was assessed by logistic regression, adjusted for site, organism, and clinical variables, and linear regression was applied to examine the association between clinical variables and TTP. Robustness was assessed by sensitivity analysis.

Results: In total 4468 participants were included in the RAPIDO. After exclusions, 3462 were analysed, with the most common organisms being coagulase-negative staphylococci (1072 patients) and Escherichia coli (861 patients); 785 patients (22.7%) died within 28 days. We found no relationship between TTP and mortality for any groups except for streptococci (odds ratio (OR) with each hour 0.98, 95%CI 0.96-1.00) and Candida (OR 1.03, 95%CI 1.00-1.05). There was large variability between organisms and sites in TTP. Fever (geometric mean ratio (GMR) 0.95, 95%CI 0.92-0.99), age (GMR per 10 years 1.01, 95%CI 1.00-1.02), and neutrophilia were associated with TTP (GMR 1.03, 95%CI 1.02-1.04).

Conclusions: Time to positivity is not associated with mortality, except in the case of Candida spp. (longer times associated with worse outcomes) and possibly streptococci (shorter times associated with worse outcomes). There was a large variation between median times across centres, limiting external validity.

Keywords: Bloodstream infection; Mortality; Prognostic marker; Sepsis; Time to positivity.

Publication types

Multicenter Study
Randomized Controlled Trial

MeSH terms

Bacteremia* / diagnosis
Bacteremia* / mortality
Candida
Escherichia coli
Humans
Prognosis
Prospective Studies
Sepsis* / diagnosis
Sepsis* / mortality
Staphylococcus
Streptococcus
Time Factors